本文選題：子宮內(nèi)膜異位癥 + 體外受精-胚胎移植�。� 參考：《上海交通大學(xué)》2015年博士論文

【摘要】：第一部子宮內(nèi)膜異位癥對(duì)體外受精-胚胎移植治療臨床結(jié)果的影響目的:回顧性比較分析子宮內(nèi)膜異位癥(EMs)合并不孕和對(duì)照組(單純輸卵管因素性不孕)行體外受精-胚胎移植(IVF-ET)治療的臨床數(shù)據(jù),探討EMs對(duì)于IVF-ET治療結(jié)局的影響。方法:選取107例腹腔鏡診斷EMs的不孕女性(其中58例為I、II期EMs,49例為III、IV期EMs)和121例對(duì)照組女性納入研究,比較兩組一般情況及IVF-ET治療結(jié)局相關(guān)指標(biāo)。結(jié)果:(1)EMs和對(duì)照組兩組患者的年齡、不孕年數(shù)、體重指數(shù)、基礎(chǔ)FSH值、HCG日E2水平和移植日子宮內(nèi)膜厚度和移植胚胎數(shù)進(jìn)行比較,差異均無(wú)統(tǒng)計(jì)學(xué)意義;(2)EMs組FSH使用總量顯著高于對(duì)照組(P0.05);(3)兩組患者的獲卵數(shù)和受精率相比無(wú)差異,但EMs組的優(yōu)質(zhì)胚胎率(P0.01)和可冷凍胚胎數(shù)(P0.05)均顯著低于對(duì)照組,臨床妊娠率和種植率在EMs組有下降趨勢(shì)但差異無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論:EMs對(duì)于IVF-ET治療的臨床結(jié)果具有不良影響。EMs致卵巢對(duì)促排卵藥物的反應(yīng)性下降,降低優(yōu)質(zhì)胚胎率和可用胚胎數(shù),使得種植率和臨床妊娠率呈現(xiàn)下降趨勢(shì)。第二部分SF-1和LRH-1在子宮內(nèi)膜異位癥卵巢顆粒細(xì)胞中的表達(dá)目的:通過(guò)測(cè)定P450芳香化酶編碼基因CYP19、CYP19 PII、孤核受體家族成員類(lèi)固醇生成因子-1(steroidogenic-1,SF-1)和肝受體類(lèi)似物-1(liver receptor homolog-1,LRH-1)在EMs卵巢顆粒細(xì)胞中的表達(dá)及其相關(guān)性,探討SF-1和LRH-1在EMs卵巢顆粒細(xì)胞P450芳香化酶表達(dá)下降機(jī)制中的可能作用。方法:選取16例腹腔鏡診斷EMs的不孕女性(其中7例為I、II期EMs,9例為III、IV期EMs)和28例對(duì)照組女性納入研究。收集IVF-ET治療中的卵泡液分離純化顆粒細(xì)胞,應(yīng)用QT RT-PCR技術(shù)檢測(cè)顆粒細(xì)胞中CYP19,CYP19 PII以及SF-1、LRH-1 m RNA水平并作比較和相關(guān)分析。結(jié)果:(1)EMs卵巢顆粒細(xì)胞中CYP19(P0.05),CYP19 PII(P0.001)以及SF-1(P0.05)、LRH-1(P0.001)m RNA的表達(dá)水平均較正常對(duì)照組降低;(2)Spearman相關(guān)分析結(jié)果顯示僅EMs組顆粒細(xì)胞中SF-1和LRH-1 m RNA的表達(dá)水平與CYP19 PII m RNA呈正相關(guān)關(guān)系(P0.05)。結(jié)論:EMs卵巢顆粒細(xì)胞中SF-1和LRH-1在轉(zhuǎn)錄水平的表達(dá)下降可部分解釋EMs性不孕卵巢反應(yīng)下降和卵子質(zhì)量受損的機(jī)制,而SF-1、LRH-1和CYP19 PII在EMs顆粒細(xì)胞中的表達(dá)下降相關(guān)性是探討EMs顆粒細(xì)胞P450芳香化酶活性下降機(jī)制的初步研究。第三部分子宮內(nèi)膜異位癥卵巢顆粒細(xì)胞SF-1基因啟動(dòng)子甲基化狀態(tài)的研究目的:通過(guò)檢測(cè)并比較EMs和正常女性卵巢顆粒細(xì)胞中SF-1基因啟動(dòng)子區(qū)5’Cp G位點(diǎn)甲基化水平探討EMs卵巢顆粒細(xì)胞中SF-1表達(dá)下降的機(jī)制。方法:應(yīng)用亞硫酸鹽測(cè)序即BSP克隆測(cè)序法(Bisulfite Sequencing PCR,BSP)檢測(cè)EMs和正常女性卵巢顆粒細(xì)胞SF-1基因啟動(dòng)子區(qū)5’Cp G位點(diǎn)甲基化水平,將測(cè)得的序列與原始序列比對(duì),統(tǒng)計(jì)和比較甲基化位點(diǎn)、數(shù)量并分析兩組甲基化程度。結(jié)果:亞硫酸鹽測(cè)序片段涵蓋SF-1基因轉(zhuǎn)錄起始位點(diǎn)附近的13個(gè)Cp G位點(diǎn)(從Cp G-84到Cp G+168),正常對(duì)照組顆粒細(xì)胞SF-1基因啟動(dòng)子區(qū)域的Cp G位點(diǎn)表現(xiàn)為差異甲基化狀態(tài),而EMs組SF-1基因啟動(dòng)子區(qū)域的整體甲基化水平顯著高于對(duì)照組(P0.05),逐個(gè)位點(diǎn)的分析顯示EMs組Cp G+7,+18,+21,+42,+54,+60,+132以及+146位點(diǎn)相較于正常對(duì)照組呈現(xiàn)高甲基化水平(P0.05);而EMs組Cp G+77,+121和+141位點(diǎn)的高甲基化水平尤為顯著(P0.001)。結(jié)論:EMs卵巢顆粒細(xì)胞SF-1基因啟動(dòng)子區(qū)5’Cp G位點(diǎn)甲基化水平顯著高于對(duì)照組,尤其是+77,+121和+141Cp G位點(diǎn),可能是EMs卵巢顆粒細(xì)胞SF-1 m RNA表達(dá)降低的機(jī)制。
[Abstract]:The effect of the first endometriosis on the clinical outcome of in vitro fertilization and embryo transfer: a retrospective comparison and analysis of the clinical data of EMs combined with infertility and the control group (simple fallopian factor infertility) in vitro fertilization and embryo transfer (IVF-ET) treatment, and to explore the effect of EMs on the outcome of IVF-ET treatment. Methods: 107 infertile women diagnosed by laparoscopy (58 with I, II EMs, 49 for III, IV EMs) and 121 in the control group were included in the study to compare the general conditions of the two groups and the related indexes of the IVF-ET treatment outcome. Results: (1) the years of age, the number of infertility, the body mass index, the base FSH value, HCG E2 level and shift of two groups of patients in the two groups were compared. The difference between the thickness of endometrium and the number of transplanted embryos was not statistically significant. (2) the total use of FSH in group EMs was significantly higher than that of the control group (P0.05); (3) the number of acquired eggs and fertilization rate in the two groups was not different, but the high quality embryo rate (P0.01) and the number of frozen embryos (P0.05) in the group of EMs were significantly lower than those in the control group, and the clinical pregnancy rate and species were significantly lower than those of the control group. There was a downward trend in the rate of implantation in the EMs group, but there was no statistical difference. Conclusion: EMs has adverse effects on the clinical outcome of IVF-ET treatment with.EMs induced ovarian hyperstimulation, reducing the quality of embryo and the number of embryos available, making the implantation rate and the clinical pregnancy rate descending. Second parts of SF-1 and LRH-1 are in the uterus. The expression and correlation of P450 aromatase encoding gene CYP19, CYP19 PII, -1 (steroidogenic-1, SF-1) and -1 (liver receptor homolog-1, LRH-1) in ovarian granulosa cells and their correlation were investigated. The possible role of the decrease mechanism of P450 aromatase expression in EMs ovarian granulosa cells. Methods: 16 cases of infertility women diagnosed by EMs were selected by laparoscopy (7 cases were I, II phase EMs, 9 cases III, IV stage EMs) and 28 control women were included in the study. The follicle fluid in IVF-ET treatment was collected and purified, and the QT RT-PCR technique was used to detect the granule cells. The levels of CYP19, CYP19 PII, SF-1, LRH-1 m RNA in granulocytes were compared and analyzed. Results: (1) the expression level of CYP19 (P0.05), CYP19 PII (CYP19 PII) in EMs ovarian granulocytes were all lower than that of the normal control group; (2) the results of correlation analysis showed that only granular cells in the group of ovarian granulocytes were only in the granular cells. There was a positive correlation between the expression level of RNA and CYP19 PII m RNA (P0.05). Conclusion: the decline of SF-1 and LRH-1 at the transcription level in the EMs ovarian granulosa cells could partly explain the mechanism of the decline of the EMs sex and the loss of the ovaries and the loss of the egg mass. Preliminary study on the mechanism of decreasing the activity of P450 aromatase in granulocyte. Third Research on the methylation status of SF-1 gene promoter in ovarian granulosa cells of endometriosis: the study of EMs ovarian granular cells by detecting and comparing the level of the 5 'Cp G site methylation in the promoter region of SF-1 gene in EMs and normal female ovarian granulosa cells Methods: the mechanism of decreasing expression of SF-1. Methods: using BSP cloning sequencing (Bisulfite Sequencing PCR, BSP) to detect the methylation level of the 5 'Cp G loci of the SF-1 gene promoter region of the ovarian granulosa cells of normal women, and to compare the measured sequences with the original sequences, to count and compare the methylation sites, and to analyze the number and analyze the two groups. The degree of methylation. Results: the sulfite sequencing fragment covers 13 Cp G loci (from Cp G-84 to Cp G+168) near the starting site of the SF-1 gene transcription site. The Cp G loci of the SF-1 gene promoter region of the normal control group are differential methylation, while the overall methylation level of the SF-1 gene promoter region of the EMs group is significantly higher than that in the control group. P0.05, the analysis of one by one showed that the EMs group Cp G+7, +18, +21, +42, +54, +60, +132, and +146 loci showed higher methylation level compared to the normal control group, and the high methylation level was particularly significant. The level was significantly higher than that in the control group, especially the +77, +121 and +141Cp G loci, which may be the mechanism of the decrease of SF-1 m RNA expression in EMs granulosa cells.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R714.8

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